P813 - TRANSGENIC UNACYLATED GHRELIN OVEREXPRESSION ENHANCES ADIPOGENIC MEDIATORS, WITH LOWER ADIPOCYTE HYPERTROPHY AND IMPROVED INSULIN RESISTANCE IN A MOUSE MODEL OF HIGH-FAT DIET INDUCED OBESITY

P813

TRANSGENIC UNACYLATED GHRELIN OVEREXPRESSION ENHANCES ADIPOGENIC MEDIATORS, WITH LOWER ADIPOCYTE HYPERTROPHY AND IMPROVED INSULIN RESISTANCE IN A MOUSE MODEL OF HIGH-FAT DIET INDUCED OBESITY

G. Gortan Cappellari^1,2, A. Semolic¹, E. Angelino³, M. Zanetti^1,2, A. Graziani³, R. Barazzoni^1,*

¹Dept. of Medical, Surgical and Health Sciences, University of Trieste, Trieste, ²School of Dietetics, University of Trieste, Pordenone, ³Medical School, Università Vita-Salute San Raffaele, Milano, Italy

Rationale: Adipose tissue morphology is strongly related to obesity-associated complications, with adipocyte hypertrophy rather than hyperplasia through adipogenesis being associated with tissue and systemic metabolic derangements. We previously observed that in high-fat diet-induced obese mice, overexpression of the unacylated form of ghrelin (UnAG) prevents adipocyte hypertrophy, with improved tissue and systemic insulin sensitivity, despite comparable high body fat and food intake. However, potential impact of UnAG on adipogenesis is unknown.

Methods: We investigated by western-blot the effects of transgenic UnAG overexpression (Tg; 30-fold plasma UnAG increase) vs. wild type (Wt) on adipose tissue DLK1, a precursor-cell proliferation modulator, EGR2, a driver of adipocyte over macrophage differentiation, and adipocyte expandability (FABP4) and lipid accumulation (ADFP) markers in male 6 week-old mice fed with high-fat (HF; 60% fat) or control diet (Con) for 16 weeks (n=6/group).

Results: HF-induced weight gain and adipose tissue mass were comparable between TgHF and WtHF, as was total food intake (all p=NS). TgHF however had lower increase of adipocyte size (p<0.05) compared to WtHF. While DLK1 levels were high in all HF mice, only TgHFD had high adipocyte EGR2 levels (all p<0.05). UnAG overexpression also prevented HFD-associated increase of adipocyte pro-hypertrophic factor FABP4 levels and increased expression of ADFP (p<0.05).

Conclusion: In a mouse model of diet-induced obesity, UnAG overexpression drives preadipocyte proliferation towards adipogenesis vs. hypertrophy, with potential to prevent adiposity-induced metabolic derangements.  These findings support UnAG-related pathways as potential targets for strategies to lower metabolic complications in patients with obesity.

Disclosure of Interest: None declared